ORIGINAL RESEARCH article
Front. Physiol.
Sec. Vascular Physiology
Integrated Transcriptomic and Proteomic Analyses Identify the TLR2–CXCR4 Axis as a Regulator of Endothelial Cell Migration under Simulated Microgravity
Provisionally accepted
- Air Force Medical University, Xi'an, China
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Simulated microgravity profoundly alters endothelial cell function, particularly by affecting cell migration. This study aimed to elucidate the molecular mechanisms underlying human umbilical vein endothelial cells migration under simulated microgravity. We first performed transcriptomic and proteomic analyses and identified 964 differentially expressed genes and 183 differentially expressed proteins, respectively, which were mainly enriched in pathways related to stress responses, signal transduction, and angiogenesis. Combined analysis of both datasets revealed four key genes—TLR2, HSPB1, RBM3, and HSPA1B—showing more than a twofold change. Further protein–protein interaction network analysis incorporating 48 endothelial migration-related genes confirmed a strong interaction between TLR2 and CXCR4, identifying TLR2 as a central hub gene. Mechanistically, we demonstrated that simulated microgravity significantly promoted endothelial cell migration through TLR2 upregulation. Subsequent experiments revealed that TLR2 activation further enhanced this pro-migratory response by increasing CXCR4 expression. Collectively, these findings identify the TLR2– CXCR4 axis as a previously unrecognized mechanosensitive signaling pathway involved in endothelial adaptation to simulated microgravity, providing novel molecular targets for therapeutic intervention against microgravity-induced vascular remodeling.
Keywords: Mg, Human umbilical vein endothelial cells (HUVECs), Transcriptomics, Proteomics, Multi-omics integration, TLR2–CXCR4 axis, endothelial cell migration
Received: 08 Sep 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Qin, Wang, Li, Pan, Wang and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuan Wang, wangcircle22@163.com
Xiqing Sun, sunxiqing@fmmu.edu.cn
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